Low vitamin D levels are linked with increased cardiovascular disease risk in young adults: a sub-study and secondary analyses from the ACTIBATE randomized controlled trial.

PURPOSE: Vitamin D deficiency is related to metabolic disturbances. Indeed, a poor vitamin D status has been usually detected in patients with cardiovascular disease (CVD). However, the relationship between vitamin D and CVD risk factors in young adults remains controversial at present. This study aimed to examine the association between circulating 25-hydroxivitamin D (25(OH)D) and CVD risk factors in young adults. METHODS: The present cross-sectional study included a cohort of 177 young adults aged 18-25 years old (65% women). 25(OH)D serum concentrations were assessed using a competitive chemiluminescence immunoassay. Fasting CVD risk factors (i.e., body composition, blood pressure, glucose metabolism, lipid profile, liver, and inflammatory markers) were determined by routine methods. A panel of 63 oxylipins and endocannabinoids (eCBs) was also analyzed by targeted metabolomics. RESULTS: Circulating 25(OH)D concentrations were inversely associated with a wide range of CVD risk factors including anthropometrical (all P ≤ 0.005), body composition (all P ≤ 0.038), glucose metabolism (all P ≤ 0.029), lipid profile (all P < 0.035), liver (all P ≤ 0.011), and pro-inflammatory biomarkers (all P ≤ 0.030). No associations of serum 25(OH)D concentrations were found with pro-inflammatory markers (all P ≥ 0.104), omega-6 and omega-3 oxylipins, nor eCBs concentrations or their analogs (all P ≥ 0.05). CONCLUSION: The present findings support the idea that 25(OH)D could be a useful predictor of CVD risk in young individuals.

Colistin plasma concentrations are not associated with better clinical outcomes in patients with pneumonia caused by extremely drug-resistant Pseudomonas aeruginosa.

IMPORTANCE: In some cases, colistin is the only treatment option for infections caused by the very drug-resistant Pseudomonas aeruginosa. However, in the past decade, there have been questions concerning its pharmacokinetics and concentration at the site of infection. In this scenario, its use in a difficult-to-treat infection like pneumonia is currently debatable. This is a clinical pharmacokinetic study of colistin in patients with multidrug-resistant P. aeruginosa pneumonia. Our findings demonstrate that colistin exposure is associated with worse clinical outcomes rather than better clinical outcomes, implying that other therapeutic options should be explored in this clinical setting.

Cryopreservation of seeds of Neonotonia wightii Wight and Arn: a strategy for conservation, dormancy breaking and preservation of nutritional status.

BACKGROUND: N. wightii (Leguminosae) is valued as a cover crop and as a potential source of protein in food insecure countries. However, plantlet establishment is limited by physical dormancy. Our previous work has shown that exposure of N. wightii seeds to cryogenic temperatures is able to overcome physical dormancy. OBJECTIVE: The current study is an extension of that work where the field performance and nutritional composition of plants regenerated from N. wightii seeds was investigated. RESULTS: It was evident that plants regenerated from cryopreserved seeds displayed faster growth rates than those from control seeds. In addition, cryopreservation did not alter the nutritional profile of plants produced from cryo-stored seeds. CONCLUSION: Collectively, the results indicate that cryopreservation serves as a suitable strategy for the preservation of seeds of N. wightii with the added benefit of also serving as a dormancy breaking mechanism upon retrieval from cryogenic temperatures. Doi.org/10.54680/fr23510110712.

Cerebral and cerebellar pseudoatrophy associated with valproic acid. Report of three pediatric cases. / Pseudoatrofia cerebral y cerebelosa asociada a ácido valproico. Descripción de tres casos pediátricos.

INTRODUCTION: Cerebral and cerebellar pseudoatrophy is a rare adverse effect of valproic acid (VPA) that we need to be aware of, due to its diagnostic and therapeutic implications. CASE REPORT: We report three cases of children between 5 and 9 years old, with epilepsy and previous normal brain magnetic resonance imaging, who were taking the drug at correct doses. Pseudoatrophy manifests subacutely with symptoms and images of cerebral and/or cerebellar atrophy, reversible after drug withdrawal. DISCUSSION AND CONCLUSIONS: This is a type of VPA-related encephalopathy, different from dose-dependent toxic encephalopathy, hyperammonaemic encephalopathy or encephalopathy related to liver failure. In children, it causes cognitive, motor, mood and behavioral deterioration, and may be accompanied by epileptic decompensation. Withdrawing the drug leads to complete clinical-radiological recovery, and reducing the dose leads to improvement.

TITLE: Pseudoatrofia cerebral y cerebelosa asociada a ácido valproico. Descripción de tres casos pediátricos.Introducción. La pseudoatrofia cerebral y cerebelosa es un efecto adverso infrecuente del ácido valproico (VPA) que debemos conocer por sus implicaciones diagnósticas y terapéuticas. Caso clínico. Presentamos tres casos de niños de entre 5 y 9 años, con epilepsia y resonancia magnética craneal previa normal, que llevaban el fármaco con dosis correctas. La pseudoatrofia se manifiesta de forma subaguda con síntomas e imagen de atrofia cerebral y/o cerebelosa, reversible tras la retirada del fármaco. Discusión y conclusiones. Se trata de un tipo de encefalopatía relacionada con VPA diferente a la encefalopatía tóxica dependiente de la dosis, la encefalopatía hiperamoniémica o la relacionada con fallo hepático. En niños, cursa con deterioro cognitivo, motor, anímico y conductual, y puede acompañarse de descompensación epiléptica. La retirada del fármaco conlleva una recuperación completa clinicorradiológica, y la disminución de dosis, una mejoría.

Pseudoatrofia cerebral y cerebelosa asociada a ácido valproico. Descripción de tres casos pediátricos / Cerebral and cerebellar pseudoatrophy associated with valproic acid. Report of three pediatric cases

Introducción La pseudoatrofia cerebral y cerebelosa es un efecto adverso infrecuente del ácido valproico (VPA) que debemos conocer por sus implicaciones diagnósticas y terapéuticas. Caso clínico Presentamos tres casos de niños de entre 5 y 9 años, con epilepsia y resonancia magnética craneal previa normal, que llevaban el fármaco con dosis correctas. La pseudoatrofia se manifiesta de forma subaguda con síntomas e imagen de atrofia cerebral y/o cerebelosa, reversible tras la retirada del fármaco. Discusión y conclusiones. Se trata de un tipo de encefalopatía relacionada con VPA diferente a la encefalopatía tóxica dependiente de la dosis, la encefalopatía hiperamoniémica o la relacionada con fallo hepático. En niños, cursa con deterioro cognitivo, motor, anímico y conductual, y puede acompañarse de descompensación epiléptica. La retirada del fármaco conlleva una recuperación completa clinicorradiológica, y la disminución de dosis, una mejoría. (AU)

INTRODUCTION Cerebral and cerebellar pseudoatrophy is a rare adverse effect of valproic acid (VPA) that we need to be aware of, due to its diagnostic and therapeutic implications. CASE REPORT We report three cases of children between 5 and 9 years old, with epilepsy and previous normal brain magnetic resonance imaging, who were taking the drug at correct doses. Pseudoatrophy manifests subacutely with symptoms and images of cerebral and/or cerebellar atrophy, reversible after drug withdrawal. Discussion and conclusions. This is a type of VPA-related encephalopathy, different from dose-dependent toxic encephalopathy, hyperammonaemic encephalopathy or encephalopathy related to liver failure. In children, it causes cognitive, motor, mood and behavioral deterioration, and may be accompanied by epileptic decompensation. Withdrawing the drug leads to complete clinical-radiological recovery, and reducing the dose leads to improvement. (AU)

Impact of methods for data selection on the day-to-day reproducibility of resting metabolic rate assessed with four different metabolic carts.

BACKGROUND AND AIMS: Accomplishing a high day-to-day reproducibility is important to detect changes in resting metabolic rate (RMR) and respiratory exchange ratio (RER) that may be produced after an intervention or for monitoring patients' metabolism over time. We aimed to analyze: (i) the influence of different methods for selecting indirect calorimetry data on RMR and RER assessments; and, (ii) whether these methods influence RMR and RER day-to-day reproducibility. METHODS AND RESULTS: Twenty-eight young adults accomplished 4 consecutive RMR assessments (30-min each), using the Q-NRG (Cosmed, Rome, Italy), the Vyntus CPX (Jaeger-CareFusion, Höchberg, Germany), the Omnical (Maastricht Instruments, Maastricht, The Netherlands), and the Ultima CardiO2 (Medgraphics Corporation, St. Paul, Minnesota, USA) carts, on 2 consecutive mornings. Three types of methods were used: (i) short (periods of 5 consecutive minutes; 6-10, 11-15, 16-20, 21-25, and 26-30 min) and long time intervals (TI) methods (6-25 and 6-30 min); (ii) steady state (SSt methods); and, (iii) methods filtering the data by thresholding from the mean RMR (filtering methods). RMR and RER were similar when using different methods (except RMR for the Vyntus and RER for the Q-NRG). Conversely, using different methods impacted RMR (all P ≤ 0.037) and/or RER (P ≤ 0.009) day-to-day reproducibility in all carts. The 6-25 min and the 6-30 min long TI methods yielded more reproducible measurements for all metabolic carts. CONCLUSION: The 6-25 min and 6-30 min should be the preferred methods for selecting data, as they result in the highest day-to-day reproducibility of RMR and RER assessments.

Electrochemical biosensor for aerobic acetate detection.

There is an increasing demand on alternatives methods to animal testing. Numerous health parameters have been already studied using in vitro devices able to mimic the essential functions of the organs, being the real-time monitoring and response to stimuli their main limitations. Regarding the health of the gut, the short chain fatty acids, and particularly acetate, have emerged as key biomarkers to evaluate gut healthiness and disease development, although the number of acetate biosensors is still very low. This article presents a microbial biosensor based on fully biocompatible materials which is able to detect acetate in aerobic conditions in the range between 11 and 50 mM, and without compromising the viability and function of either bacteria (>90% viability) or mammalian cells (>80% viability). The detection mechanism is based on the metabolism of acetate by Escherichia coli bacteria immobilized on the transducer surface. Ferricyanide is used as a redox mediator to transfer electrons from the acetate metabolism in the bacterial cells to the transducer. High bacterial concentrations are immobilized in the transducer surface (109 cfu mL-1) by electrodeposition of conductive alginate hydrogels doped with reduced graphene oxide. The results show successful outcomes to exploit bacteria as a biosensing tool, based on the use of inkjet printed transducers, biocompatible materials and cell entrapment technologies.

Efficacy and safety of dolutegravir/rilpivirine in real-world clinical practice. GeSIDA study 1119.

INTRODUCTION: Dolutegravir/rilpivirine (DTG/RPV) is an effective antiretroviral (ART) regimen endorsed by clinical trials as a switch therapy. The aim of our study was to analyse the efficacy and safety of DTG/RPV in real-world clinical practice. METHODS: Observational, multicentre study of patients who started DTG/RPV. Efficacy, adverse events and metabolic changes at 48 weeks were analysed. RESULTS: A total of 348 patients were included; median time of HIV infection was 21.1 years, 33.7% were AIDS cases; median nadir CD4 was 160 cells/µL; 90.5% had received ≥3 lines of ART and 179 (53.8%) had prior virological failure. Convenience (43.5%), toxicity/intolerance (28.4%) and interactions (17.0%) were the main reasons for starting DTG/RPV. Previous regimens were protease inhibitors (PI) (31.6%), non-nucleoside reverse transcriptase inhibitors (NNRTI) (20.4%) and integrase strand transfer inhibitors (INSTI) (14.9%). Efficacy (HIV-RNA <50 copies/mL) at 48 weeks was 89.7% (95% CI 86.1-92.6) by intention-to-treat (ITT) and 94.2% (95% CI 91.3-96.4) by on treatment (OT); 10 patients (3.1%) were not suppressed (3 had abandoned ART). There was a mean decrease in triglycerides, total cholesterol, low-density lipoprotein-cholesterol, glutamic-pyruvic transaminase (GPT), gamma-glutamyl transferase (GGT) and alkaline phosphatase; creatinine increased with a decrease in glomerular filtration rate. CONCLUSIONS: This study confirms the effectiveness, tolerability and safety of DTG/RPV in real-world clinical practice in a different population from clinical trials, with many years of infection, low CD4 nadir, several previous treatment lines, more than half with virological failures, and one-third diagnosed with AIDS. The switch to DTG/RPV was safe with few discontinuations due to adverse effects. Modifications of the lipid and liver profiles were favourable. There were no relevant changes in kidney function.

Treatment of COVID-19 pneumonia with low-dose radiotherapy plus standard of care versus standard of care alone in frail patients : The SEOR-GICOR IPACOVID comparative cohort trial.

PURPOSE: To assess the efficacy of lung low-dose radiotherapy (LD-RT) in the treatment of patients with COVID-19 pneumonia. MATERIALS AND METHODS: Ambispective study with two cohorts to compare treatment with standard of care (SoC) plus a single dose of 0.5 Gy to the whole thorax (experimental prospective cohort) with SoC alone (control retrospective cohort) for patients with COVID-19 pneumonia not candidates for admission to the intensive care unit (ICU) for mechanical ventilation. RESULTS: Fifty patients treated with LD-RT were compared with 50 matched controls. Mean age was 85 years in both groups. An increase in arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (PAFI) in the experimental LD-RT-treated group compared to the control group could not be found at 48 h after LD-RT, which was the primary endpoint of the study. However, PAFI values significantly improved after 1 month (473 vs. 302 mm Hg; p < 0.0001). Pulse oxymetric saturation/fraction of inspired oxygen (SAFI) values were also significantly higher in LD-RT-treated patients than in control patients at 1 week (405 vs. 334 mm Hg; p = 0.0157) and 1 month after LD-RT (462 vs. 326 mm Hg; p < 0.0001). All other timepoint measurements of the respiratory parameters were similar across groups. Patients in the experimental group were discharged from the hospital significantly earlier (23 vs. 31 days; p = 0.047). Fifteen and 26 patients died due to COVID-19 pneumonia in the experimental and control cohorts, respectively (30% vs. 48%; p = 0.1). LD-RT was associated with a decreased odds ratio (OR) for 1­month COVID-19 mortality (OR = 0.302 [0.106-0.859]; p = 0.025) when adjusted for potentially confounding factors. Overall survival was significantly prolonged in the LD-RT group compared to the control group (log-rank p = 0.027). No adverse events related to radiation treatment were observed. CONCLUSION: Treatment of frail patients with COVID-19 pneumonia with SoC plus single-dose LD-RT of 0.5 Gy improved respiratory parameters, reduced the period of hospitalization, decreased the rate of 1­month mortality, and prolonged actuarial overall survival compared to SoC alone.

The genus Microcotyle in Mediterranean scorpaenoids (Teleostei), including the description of Microcotyle merche n. sp. from Helicolenus dactylopterus (Delaroche, 1809).

More than 65 species of the genus Microcotyle Van Beneden & Hesse, 1863, have been described to date, most of them infecting Perciformes. Among the scorpaenoids (Perciformes, formerly Scorpaeniformes) the species of the genus Microcotyle parasitize sebastids and scorpaenids worldwide. In this study, we provide new morphological and molecular data for Microcotyle spp. in sebastids and scorpaenids from the Western Mediterranean and north-east Atlantic. Specimens of Helicolenus dactylopterus (Delaroche, 1809) (n = 107) and Scorpaena spp. (n = 107) were examined and their microcotylid specimens morphologically and molecularly characterized. Microcotyle merche n. sp. ex H. dactylopterus and specimens of Microcotyle algeriensis Ayadi, Gey, Justine & Tazerouti, 2016 from a new host and locality (Scorpaena scrofa from the north-east Atlantic) are herein described. Both species are phylogenetically close, but their morphology is markedly different mostly because the anterior lobe of the haptor present in other Microcotyle species is almost absent in M. algeriensis. Findings of M. merche n. sp. in the Mediterranean also excludes the presence of Microcotyle sebastis in this sea, encouraging the review of the exceptionally large host range and geographical distribution of this species.

Pharmacokinetics/pharmacodynamics and therapeutic drug monitoring of ceftazidime/avibactam administered by continuous infusion in patients with MDR Gram-negative bacterial infections.

BACKGROUND: Therapeutic drug monitoring (TDM) of ß-lactams in critically ill patients has been correlated with better clinical outcomes. Evidence on TDM of newer ß-lactams such as ceftazidime/avibactam administered by continuous infusion (CI) is very limited. OBJECTIVES: To describe our experience with TDM of ceftazidime/avibactam and pharmacokinetic/pharmacodynamic (PK/PD) target attainment in patients with MDR bacterial infections. Clinical outcomes of ceftazidime/avibactam administered by CI were also assessed. METHODS: Patients treated with ceftazidime/avibactam administered by CI and undergoing TDM of ceftazidime plasma concentrations were included. Blood samples were obtained as part of the TDM program. The PK/PD therapeutic target of ceftazidime/avibactam was defined as 100%fT > 4 × MIC of the causative pathogen, and 100%fT > 10 × MIC was considered overexposure. Dose changes were made according to the TDM results. RESULTS: Thirty-one patients were included. Ceftazidime/avibactam total daily doses ranged from 1 g/0.25 g to 6 g/1.5 g. Twenty-six patients (83.9%) achieved a 100%fT > 4 × MIC, 15 (48.4%) of which were overexposed (100%fT > 10 × MIC). Dose reduction was suggested in 16/28 (57.1%) patients and dose maintenance in 12/28 (42.9%). Overall clinical cure was observed in 21 (67.7%) patients, and 18 of these (85.7%) achieved a 100%fT > 4 × MIC. CONCLUSIONS: Administering ceftazidime/avibactam by CI enabled the desired PK/PD target to be achieved in a large proportion of patients, even at lower doses than those recommended for a 2 h extended infusion. We suggest that the use of CI with TDM may be a useful tool for reducing initial doses, which could help to reduce antimicrobial-related adverse effects and treatment costs.

Acute phase characteristics and long-term complications of pulmonary embolism in COVID-19 compared to non-COVID-19 cohort: a large single-centre study.

BACKGROUND: To compare the severity of pulmonary embolism (PE) and the long-term complications between patients with and without COVID-19, and to investigate whether the tools for risk stratification of death are valid in this population. METHODS: We retrospectively included hospitalized patients with PE from 1 January 2016 to 31 December 2022. Comparisons for acute episode characteristics, risk stratification of the PE, outcomes, and long-term complications were made between COVID and non-COVID patients. RESULTS: We analyzed 116 (27.5%) COVID patients and 305 (72.4%) non-COVID patients. In patients with COVID-19, the traditional risk factors for PE were absent, and the incidence of deep vein thrombosis was lower. COVID patients showed significantly higher lymphocyte count, lactate dehydrogenase, lactic acid, and D-dimer levels. COVID patients had PE of smaller size (12.3% vs. 25.5% main pulmonary artery, 29.8% vs. 37.1% lobar, 44.7% vs. 29.5% segmental and 13.2% vs. 7.9% subsegmental, respectively; p < 0.001), less right ventricular dysfunction (7.7% vs. 17.7%; p = 0.007) and higher sPESI score (1.66 vs. 1.11; p < 0.001). The need for mechanical ventilation was significantly higher in COVID patients (8.6% vs. 1.3%; p < 0.001); However, the in-hospital death was less (5.2% vs. 10.8%; p = 0.074). The incidence of long-term complications was lower in COVID cohort (p < 0.001). PE severity assessed by high sPESI and intermediate and high-risk categories were independently associated with in-hospital mortality in COVID patients. CONCLUSION: The risk of in-hospital mortality and the incidence of long-term complications were lower in COVID-19. The usual tools for risk stratification of PE are valid in COVID patients.

On the uptake of cationic liposomes by cells: From changes in elasticity to internalization.

In this study, we assessed the capacity of a previously reported engineered liposomal formulation, which had been tested against model membranes mimicking the lipid composition of the HeLa plasma membrane, to fuse and function as a nanocarrier in cells. We used atomic force microscopy to observe physicochemical changes on the cell surface and confocal microscopy to determine how the liposomes interact with cell membranes and released their load. In addition, we performed viability assays using methotrexate as an active drug to obtain proof of concept of the formulation´s capacity to function as a drug delivery-system. The interaction of engineered liposomes with living cells corroborates the information obtained using model membranes and supports the capacity of the engineered liposomal formulation to serve as a potential nanocarrier.

Studying Lipid Membrane Interactions of a Super-Cationic Peptide in Model Membranes and Living Bacteria.

The super-cationic peptide dendrimers (SCPD) family is a valuable class of antimicrobial peptide candidates for the future development of antibacterial agents against multidrug-resistant gram-negative bacteria. The deep knowledge of their mechanism of action is a major challenge in research, since it may be the basis for future modifications/optimizations. In this work we have explored the interaction between SCPD and membranes through biophysical and microbiological approaches in the case of the G1OLO-L2OL2 peptide. Results support the idea that the peptide is not only adsorbed or close to the surface of the membrane but associated/absorbed to some extent to the hydrophobic-hydrophilic region of the phospholipids. The presence of low concentrations of the peptide at the surface level is concomitant with destabilization of the cell integrity and this may contribute to osmotic stress, although other mechanisms of action cannot be ruled out.

Pulmonary mixed squamous and glandular papilloma: diagnostic challenges of a rare lesion when the clock is ticking. How to avoid interpretation mistakes.

Pulmonary mixed squamous and glandular papillomas (MSCGPs) are rare, benign neoplasms with peculiar clinical and histological features. However, on occasion, they can present certain characteristics that overlap with other neoplasms including carcinomas. Recognising these features is hence important for treatment purposes. Molecular studies can sometimes help in further characterisation, although they should not guide the diagnosis which ultimately relies on morphology.We report a challenging case of MSCGP with unusual features, received during intraoperative consultation. We highlight the subtle morphological features to help avoid overcalling a benign lesion as malignant.

Hemorragia intracerebral fatal asociada al síndrome de trombosis con trombocitopenia tras la vacuna ChAdOx1-S / Fatal intracerebral haemorrhage associated with thrombosis with thrombocytopenia syndrome after ChAdOx1-S vaccine

Introducción: La pandemia por COVID-19 ha tenido un impacto devastador en la salud, la sociedad y la economía en el mundo. Por ello, las vacunas contra el coronavirus del síndrome respiratorio agudo grave 2 (SARS-CoV-2) han surgido como medida importante para combatir la pandemia. ChAdOx1-S (Oxford-AstraZeneca) es una vacuna vectorizada por adenovirus que expresa la proteína de espiga del SARS-CoV-2. Se han notificado varios casos de trombosis y trombocitopenia inusuales tras la ChAdOx1-S que imitan la trombocitopenia autoinmune inducida por heparina. Esta situación se denomina síndrome de trombosis con trombocitopenia (STT), y se han descrito casos de hemorragia intracerebral secundaria. Caso clínico: Presentamos un caso de hemorragia intracerebral tras la vacunación con ChAdOx1-S. Una paciente de mediana edad sin antecedentes médicos de interés fue atendida en urgencias 16 días después de la primera dosis de ChAdOx1-S con una hemiplejía izquierda de inicio repentino y una cefalea opresiva holocraneal grave. No recibió heparina los 100 días anteriores. El análisis de sangre mostró trombocitopenia moderada y en la tomografía computarizada se observó una hemorragia lobar frontal derecha sin trombosis en la venografía por tomografía computarizada. Se confirmó la presencia de anticuerpos contra el factor 4 de las plaquetas en la sangre. La paciente presentó un síndrome de hipertensión intracraneal resistente al tratamiento y falleció tres semanas después. Conclusiones: El STT es un efecto adverso infrecuente de la vacuna ChAdOx1-S que se define por la presencia de trombosis en localizaciones infrecuentes. En nuestro caso, describimos una hemorragia intracerebral espontánea secundaria a la trombocitopenia desencadenada por el STT. Representa una presentación clínica poco frecuente del STT.(AU)

INTRODUCTION: The COVID-19 pandemic has had a devastating impact on health, society and economics worldwide. Therefore, vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have recently emerged as an important measure to fight the pandemic. ChAdOx1-S (Oxford-AstraZeneca) is an adenovirus-vectored vaccine that expresses the SARS-CoV-2 spike protein. It shows an acceptable safety profile. Nevertheless, several cases of unusual thrombosis and thrombocytopenia have been reported after initial vaccination with ChAdOx1-S mimicking autoimmune heparin-induced thrombocytopenia. This condition has been called thrombosis with thrombocytopenia syndrome (TTS) and complications such as intracerebral haemorrhage have been described. CASE REPORT: We present a case of intracerebral haemorrhage after ChAdOx1-S vaccination. Middle-aged patient with no prior medical history was seen in the emergency room 16 days after the first dose of ChAdOx1-S vaccine with sudden onset left hemiplegia and severe holocranial oppressive headache. She did not receive heparin treatment in the previous 100 days. Blood test showed moderate thrombocytopenia and a right frontal lobar haemorrhage was seen on computed tomography scan, computed tomography venography was negative for thrombosis. The presence of antibodies against platelet factor 4 was confirmed. The patient’s neurological condition progressively worsened. She developed a treatment resistant intracranial hypertension syndrome and she died three weeks later. CONCLUSIONS: TTS is a rare adverse effect of ChAdOx1-S vaccine, defined by the presence of thrombosis in uncommon locations. In our case we report an spontaneous intracerebral haemorrhage probable due to the thrombocytopenia related to probable TTS. It represents a rare clinical presentation of TTS.(AU)

Fatal intracerebral haemorrhage associated with thrombosis with thrombocytopenia syndrome after ChAdOx1-S vaccine. / Hemorragia intracerebral fatal asociada al síndrome de trombosis con trombocitopenia tras la vacuna ChAdOx1-S.

INTRODUCTION: The COVID-19 pandemic has had a devastating impact on health, society and economics worldwide. Therefore, vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have recently emerged as an important measure to fight the pandemic. ChAdOx1-S (Oxford-AstraZeneca) is an adenovirus-vectored vaccine that expresses the SARS-CoV-2 spike protein. It shows an acceptable safety profile. Nevertheless, several cases of unusual thrombosis and thrombocytopenia have been reported after initial vaccination with ChAdOx1-S mimicking autoimmune heparin-induced thrombocytopenia. This condition has been called thrombosis with thrombocytopenia syndrome (TTS) and complications such as intracerebral haemorrhage have been described. CASE REPORT: We present a case of intracerebral haemorrhage after ChAdOx1-S vaccination. Middle-aged patient with no prior medical history was seen in the emergency room 16 days after the first dose of ChAdOx1-S vaccine with sudden onset left hemiplegia and severe holocranial oppressive headache. She did not receive heparin treatment in the previous 100 days. Blood test showed moderate thrombocytopenia and a right frontal lobar haemorrhage was seen on computed tomography scan, computed tomography venography was negative for thrombosis. The presence of antibodies against platelet factor 4 was confirmed. The patient's neurological condition progressively worsened. She developed a treatment resistant intracranial hypertension syndrome and she died three weeks later. CONCLUSIONS: TTS is a rare adverse effect of ChAdOx1-S vaccine, defined by the presence of thrombosis in uncommon locations. In our case we report an spontaneous intracerebral haemorrhage probable due to the thrombocytopenia related to probable TTS. It represents a rare clinical presentation of TTS.

TITLE: Hemorragia intracerebral fatal asociada al síndrome de trombosis con trombocitopenia tras la vacuna ChAdOx1-S.Introducción. La pandemia por COVID-19 ha tenido un impacto devastador en la salud, la sociedad y la economía en el mundo. Por ello, las vacunas contra el coronavirus del síndrome respiratorio agudo grave 2 (SARS-CoV-2) han surgido como medida importante para combatir la pandemia. ChAdOx1-S (Oxford-AstraZeneca) es una vacuna vectorizada por adenovirus que expresa la proteína de espiga del SARS-CoV-2. Se han notificado varios casos de trombosis y trombocitopenia inusuales tras la ChAdOx1-S que imitan la trombocitopenia autoinmune inducida por heparina. Esta situación se denomina síndrome de trombosis con trombocitopenia (STT), y se han descrito casos de hemorragia intracerebral secundaria. Caso clínico. Presentamos un caso de hemorragia intracerebral tras la vacunación con ChAdOx1-S. Una paciente de mediana edad sin antecedentes médicos de interés fue atendida en urgencias 16 días después de la primera dosis de ChAdOx1-S con una hemiplejía izquierda de inicio repentino y una cefalea opresiva holocraneal grave. No recibió heparina los 100 días anteriores. El análisis de sangre mostró trombocitopenia moderada y en la tomografía computarizada se observó una hemorragia lobar frontal derecha sin trombosis en la venografía por tomografía computarizada. Se confirmó la presencia de anticuerpos contra el factor 4 de las plaquetas en la sangre. La paciente presentó un síndrome de hipertensión intracraneal resistente al tratamiento y falleció tres semanas después. Conclusiones. El STT es un efecto adverso infrecuente de la vacuna ChAdOx1-S que se define por la presencia de trombosis en localizaciones infrecuentes. En nuestro caso, describimos una hemorragia intracerebral espontánea secundaria a la trombocitopenia desencadenada por el STT. Representa una presentación clínica poco frecuente del STT.

The UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix.

Usual interstitial pneumonia (UIP) is a histological pattern characteristic of idiopathic pulmonary fibrosis (IPF). The UIP pattern is patchy with histologically normal lung adjacent to dense fibrotic tissue. At this interface, fibroblastic foci (FF) are present and are sites where myofibroblasts and extracellular matrix (ECM) accumulate. Utilizing laser capture microdissection-coupled mass spectrometry, we interrogated the FF, adjacent mature scar, and adjacent alveoli in 6 fibrotic (UIP/IPF) specimens plus 6 nonfibrotic alveolar specimens as controls. The data were subjected to qualitative and quantitative analysis and histologically validated. We found that the fibrotic alveoli protein signature is defined by immune deregulation as the strongest category. The fibrotic mature scar classified as end-stage fibrosis whereas the FF contained an overabundance of a distinctive ECM compared with the nonfibrotic control. Furthermore, FF were positive for both TGFB1 and TGFB3, whereas the aberrant basaloid cell lining of FF was predominantly positive for TGFB2. In conclusion, spatial proteomics demonstrated distinct protein compositions in the histologically defined regions of UIP/IPF tissue. These data revealed that FF are the main site of collagen biosynthesis and that the adjacent alveoli are abnormal. This essential information will inform future mechanistic studies on fibrosis progression.